Based on a retrospective review of the historical pediatric cases hospitalized in the First Affiliated Hospital of Xiamen University from January 1st, 2011 to December 31st, 2021.

A total of 50 pediatric cases accepted by the pediatric department of the First Affiliated Hospital of Xiamen University were diagnosed with B. cepacia infection.

The inclusion criteria were: (1) patients under 14 years old, (2) Positive B. cepacia cultures of body fluid samples, central venous catheter tips, or endotracheal tube tips. The following criteria were excluded: the patient had a definitive cystic fibrosis diagnosis.

In accordance with the Manual of Clinical Microbiology (6, 7), the following body fluid samples were collected: endotracheal aspirates, deep sputum, bronchoalveolar lavage (BAL), blood (from peripheral veins or central venous catheters), cerebrospinal fluid, and urine. Moreover, demographics, clinical and laboratory data (prognosis, complications) were documented for each patient.

Infections caused by nosocomial bloodstream bacteria were defined by the presence of a positive blood culture in patients who had been hospitalized for more than 48 h. A patient was considered to have a health care-associated bloodstream infection if a positive blood culture was observed from the patient at the time of hospital admission or within 48 h if any of the following conditions were fulfilled: (1). The 30 days before the bloodstream infection, the patient received home intravenous therapy, wound care or specialized nursing care from a health care agency, family, or friends. Patients whose only home therapy was oxygen use were excluded. (2). Attended a hospital or hemodialysis clinic or received intravenous chemotherapy in the 30 days before the bloodstream infection. (3). Was hospitalized in an acute care hospital for two or more days in the 90 days before the bloodstream infection. (4). Resided in a nursing home or long-term care facility.

Community-acquired bloodstream infection was defined by a presence of positive blood culture observed at the time of hospital admission or within the 48 h after admission. Patients meeting the criteria will be considered as community associated infection (8).

In addition, definite catheter-related bloodstream infection was defined as a presence of positive blood culture, along with a presence of positive catheter tip culture yielding the same species of microorganism, or the growth of the same pathogen from blood cultures of the CVC and a peripheral vein, with positive values for the differential time to positivity (9).

Community-acquired pneumonia (CAP) is an infection acquired outside of a hospital. Infection acquired after at least 48 h in the hospital is defined as hospital-acquired pneumonia (HAP). Ventilator-associated pneumonia (VAP) is defined as a subcategory of HAP that occurs in patients receiving mechanical ventilation. Infection acquired in low-acuity healthcare settings such as nursing homes and dialysis centers is known as healthcare-associated pneumonia (HCAP) (10).

Samples were inoculated onto eosin methylene blue agar (Autobio Diagnostics Co Ltd.) and Colombian blood agar medium (Autobio Diagnostics Co Ltd.). All inoculated plates were incubated in Thermo M3111 incubator (Thermo Inc.). Pathogen identifications were performed using the Vitek MS-CHCA (BioMérieux Inc.) and Vitek-MS automated microbial identification system (BioMérieux Inc.).

Antimicrobial susceptibility testing of B.cepacia isolates were determined by the automated VITEK 2 compact microbiology analyzer (BioMérieux Inc., France). Results were interpreted as sensitive, intermediate and resistance based on the Clinical and Laboratory Standards Institute's (CLSI) criterias (11–21). For statistical analysis purpose, “intermediate” sensitivity results of bacterial isolates were grouped to “resistant” sensitivity results. The quality control strains of pathogen identification were E.coli ATCC 25922 strains (National Center for Clinical Laboratories, China) and E.coli ATCC 8739 strains (Biomerieux Inc., France). For quality control of susceptibility tests, Pseudomonas aeruginosa ATCC 27853 strains (National Center for Clinical Laboratories, China) were used.

BioMerieux mini Vidas automated immunoassay analyzer (BioMérieux Inc.) and procalcitonin (PCT) kit were used to detect serum PCT. C-reactive protein (CRP) was detected by VITROS 5,1 FS analyzer (Ortho-Clinical Diagnostics) using the manufacturer's reagents.

Statistical analyses were performed using SPSS software (version 22.0; IBM SPSS, Inc., Chicago, IL, USA). Discrete numbers and percentages were used to represent categorical variables. A mean and standard deviation (SD) were used to present continuous variables. T test was used to conduct a statistical comparison, with significance determined by a p value < 0.05.

In this study, the baseline characteristics, clinical characteristics, laboratory findings and antimicrobial susceptibility were investigated in 50 cases of B. cepacia infection. Furthermore, we summarized empirical antibiotic treatments and antibiotic treatments after receiving an antibiogram. The prevalence and prognosis of infections caused by B. cepacia was investigated among non-CF pediatric patients with or without the underlying disease.

During the study period, 50 pediatric patients were diagnosed with B. cepacia infection, 18 (36%) of whom were female and the median age was 15 months (one day, 123 months). In this patient cohort, 68% had underlying diseases. The most common underlying disease was cardiovascular disease (23.5%), followed by respiratory diseases (17.6%), nervous system disease (14.7%) and neoplastic disease (14.7%). There were six patients with respiratory diseases, including two cases of tracheomalacia and tracheal stenosis, and one case of idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. One patient with tracheomalacia was tracheotomy dependent. Patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis were both treated with long-term oral prednisone. There were five patients with neurological disorders, including one each with spinal muscular atrophy and mitochondrial encephalomyopathy, central hypoventilation syndrome, Charcot-Marie-Tooth disease, intracranial hemorrhage with Ommaya capsule implantation. At the onset of infection with B. cepacia, these five patients were intubated and ventilated. The demographic characteristics of the patients were listed in Table 1 below.

The clinical characteristics of 50 pediatric cases having B. cepacia infection were tabulated in Table 2. Upon onset of B. cepacia infection, 42 (84%) children were in the ICU, 33 (66%) underwent endotracheal intubation, and 32 (64%) received a central venous catheter. Four cases (8%) were health care-associated infections, and 46 (92%) were hospital-acquired infections. Infection with B. cepacia most commonly occurs in the respiratory tract (68%), blood (20%), and urinary tract (12%).

Pediatric patients with B. cepacia infection had elevated CRP and PCT levels, as well as an increase in neutrophils. A statistically significant difference between patients with and without underlying diseases was not found in the experimental results shown in Table 3.

The antimicrobial susceptibility testing results of B. cepacia isolated were shown in Table 4. It was found that 95.65% and 88.68% of B. cepacia isolates were susceptible to ceftazidime and trimethoprim-sulfamethoxazole (TMP-SMX). Susceptibility rates for meropenem, cefepime, and levofloxacin were 82.98%, 77.78%, 53.85%, respectively. Isolates of B. cepacia showed low susceptibility to cefoperazone-sulbactam (22.22%), ceftriaxone (22.22%), tigecycline (20%), and ticacillin/potassium clavulanate (1%). A susceptibility test revealed 100% resistance to nitrofurantoin and tobramycin.

The empirical antibiotic treatments and adjustment of antibiotics after the antibiogram available were shown in Table 5. Empiric antibiotic regimens were adjusted in 30 cases. The most common empiric antibiotic used was cefoperazone-sulbactam (30%), followed by meropenem (28%), cefepime (8%) and piperacillin-tazobactam (8%). Meropenem was the most effective empiric antibiotics used in this research. Meropenem was used in 20 cases of patients (15 cases used alone, three cases combined with ceftazidime, one case combined with tigecycline, one case combined with TMP-SMX). In our study, five cases were treated with meropenem in combination with other antibiotics. Of all these five treatments were started with meropenem, and the second antibiotic was added according to the result of drug susceptibility test when fever persisted and clinical situation of patient continued worsening after 3 days' meropenem therapy. Only one out of the five strains was intermediate to meropenem and the others were sensitive to meropenem. In this group of 20 patients, 13 improved, four gave up treatment, and four died. The other antibiotics used after the available antibiogram were piperacillin tazobactam (12%), cefepime(10%), TMP-SMX (8%), cefoperazone-sulbactam (8%), ceftazidime (6%) ceftriaxone (4%), levofloxacin (2%) and others (8%) presented in Table 6.

Almost all patients had good responses to definitive antibiotic therapy. Furthermore, eight patients withdrew from treatment because their caregivers couldn't afford the out-of-pocket cost burden. The average length of hospital stay of 50 patients was 34.6 days, and the average length of ICU stay for 41 patients was 26.8 days. After treatment, 38 patients improved, eight patients were loss to follow-up, and four patients died. Two CGD patients both had B. cepacia bloodstream infection died of multiple organ failure without the presence of macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH). One case of severe viral encephalitis died of multiple organ failure. After intracranial hemorrhage during extracorporeal membrane oxygenation (ECMO) treatment, one patient with severe adenovirus pneumonia died of cerebral herniation, as shown in Table 7.